Research activities of the
Neisseria unit are in the field of the molecular
epidemiology and pathogenesis of infections due to Neisseria
meningitidis(Nm).

1. The pathogenesis of meningococcal
infections. Nm is a common host of the human rhinopharynx.
Invasive infection is a rare event that implies bacterial
crossing of the epithelial and endothelial barriers to provoke
bacteremia. We studied the regulation of the expression of
bacterial structures such as the pili and the capsule during
Nm-host cells interactions. However, functional genomic studies
are impaired by the lack of laboratory animal model. We have
developed a mouse model of sequential respiratory infection with
the influenza A virus and Nm that reproduces meningococcemia.
Also, infection of transgenic mice expressing the human
transferrin, which is essential for iron uptake by Nm, offers the
possibility to quantify experimental infection in this original
model of meningococcemia and meningitis.

2. Inflammation and virulence. The
meningococcal disease, resulting from blood borne invasion of the
host’s body by replicating bacteria, is dominated by the
activation of pro-inflammatory cytokines. Nm lipooligosaccharide
(LOS) is a potent endotoxin. However, the study of specific LOS
mutants has revealed that other bacterial products (such as
peptidoglycan) also play an important role in stimulating
inflammatory responses and virulence.

3. Impaired virulence of N.
meningitidisstrains with reduced susceptibility to penicillin
G. Such isolates are altered in the gene penAencoding the
penicillin-binding protein (PBP) 2. Studies of PBP2 variants show
that they have modified peptidoglycan as well as impaired
virulence and inflammatory properties.

4. Evaluating PBP2 as new vaccine
candidates. PBP2 share conserved N and C terminal domains in
either penicillin susceptible or strains. PBP2 is naturally
immunogenic, as assessed from serological studies in . Both
passive and active immunization of mice with PBP2 induce
protection against Nm challenge.

4.1. Tailor made vaccines. There is a
strong need of vaccineam serogr B, promineninand in tAme outsicle
(OMV) protein-based vaccines to serogroup B epidemic strains has
been effectively applied in Cuba, Norway and New Zealand. In
France, an outbreak of meningoccal disease, dominated by Nm
B:14:P1.7,16, ST-32 strains, persists since 1997, in Normandy.
the Normandy strain is to the vaccine strain B:15 :P1.7,16/ ST-32
used in Norway, we tested the bactericidal activities of from
Norwegian vaccinees and found equivalent bactericidal titers to
both strains. These results helped the health authorities to
decide to vaccinate the exposed children.bactersample of 250
vaccinthis vaccination.

5. Reference activities. In France,
the annual incidence remains stable at <1/100,000. Serogroup B
remains the most frequent (>6%), followed by serogroup C (2%),
serogroup W135 (3), and serogroup Y (3.6%)Our laboratory also
participates actively in the efforts of the European Monitoring
Group on Meningococci. We have led several inter laboratory
studies to standardize the techniques of detection and typing of
Nm. We are currently conducting a large study of penA sequencing
and have already included >1500 isolates, among which 139
different alleles have been identified to date, in a database
accessible through the internet (http://neisseria.org/nm/typing/penA/).